Decreased E-cadherin augments beta-catenin nuclear localization: studies in breast cancer cell lines
| Autor: | S Z, Yang, N, Kohno, A, Yokoyama, K, Kondo, H, Hamada, K, Hiwada |
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| Rok vydání: | 2001 |
| Předmět: |
Cell Nucleus
Genes APC Reverse Transcriptase Polymerase Chain Reaction Blotting Western Cell Membrane Mucin-1 Genes myc Gene Expression Breast Neoplasms Cadherins Precipitin Tests Proto-Oncogene Mas Immunoenzyme Techniques Blotting Southern Cytoskeletal Proteins Trans-Activators Tumor Cells Cultured Humans Female Cell Division beta Catenin DNA Primers |
| Zdroj: | International journal of oncology. 18(3) |
| ISSN: | 1019-6439 |
| Popis: | We showed that the YMB-1-derived breast cancer cell line YMB-S, which proliferates in suspension without aggregation, exhibits complete loss of cell-cell adhesion despite the presence of E-cadherin-catenin complex and expression of free beta-catenin in the cytoplasm. Here, we describe beta-catenin gene regulation, interaction with E-cadherin, immunocytochemical localization, and their relation to growth rate in the YMB-1-derived cell line YMB-A, which forms tight junctions and displays anchorage-dependent growth. YMB-A cells proliferated more slowly than YMB-S cells. E-cadherin and APC gene product expression in YMB-A cells was significantly higher than that in YMB-S cells, whereas expression of beta-catenin, MUC1, and c-myc was lower in YMB-A cells than in YMB-S cells. According to immunocytochemical analysis, beta-catenin in YMB-A cells displayed membranous or submembranous localization, indicating that beta-catenin is mostly tethered to E-cadherin. Inhibition of E-cadherin expression in YMB-A cells by an antisense oligonucleotide did not change expression of whole cell beta-catenin protein, but increased nuclear beta-catenin protein level, c-myc expression, and cell growth rate. These results suggest that decreased expression of E-cadherin and APC and increased amount of beta-catenin in YMB-S cells lead to accumulation of beta-catenin in the nucleus, activate beta-catenin-LEF/TCF signaling pathway, and trigger c-myc proto-oncogene expression. c-Myc overexpression in breast cancer may be related to activated Wnt independent beta-catenin-LEF/TCF signaling. |
| Databáze: | OpenAIRE |
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